Journal
BLOOD
Volume 120, Issue 23, Pages 4609-4620Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2012-05-428896
Keywords
-
Categories
Funding
- Deutsche Forschungsgemeinschaft [KU1315/5-2, KU1315/7-1]
- German Jose Carreras Leukemia Foundation [F 05/01]
- Associazione Italiana Ricerca sul Cancro [MCO 10007]
- Ms Livia Benedetti (fellowship)
Ask authors/readers for more resources
The pathogenesis of classical Hodgkin lymphoma (cHL), the most common lymphoma in the young, is still enigmatic, largely because its Hodgkin and Reed-Sternberg (HRS) tumor cells are rare in the involved lymph node and therefore difficult to analyze. Here, by overcoming this technical challenge and performing, for the first time, a genome-wide transcriptional analysis of microdissected HRS cells compared with other B-cell lymphomas, cHL lines, and normal B-cell subsets, we show that they differ extensively from the usually studied cHL cell lines, that the lost B-cell identity of cHLs is not linked to the acquisition of a plasma cell-like gene expression program, and that Epstein-Barr virus infection of HRS cells has a minor transcriptional influence on the established cHL clone. Moreover, although cHL appears a distinct lymphoma entity overall, HRS cells of its histologic subtypes diverged in their similarity to other related lymphomas. Unexpectedly, we identified 2 molecular subgroups of cHL associated with differential strengths of the transcription factor activity of the NOTCH1, MYC, and IRF4 proto-oncogenes. Finally, HRS cells display deregulated expression of several genes potentially highly relevant to lymphoma pathogenesis, including silencing of the apoptosis-inducer BIK and of INPP5D, an inhibitor of the PI3K-driven oncogenic pathway. (Blood. 2012; 120(23):4609-4620)
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available